METHODS FOR THE PREPARATION OF HIV ATTACHMENT INHIBITOR PIPERAZINE PRODRUG COMPOUND

摘要

A method for making the compound;;is set forth utilizing the starting material;

主权项

1. A process for preparing the compound 13awhich comprises:
(1) reacting the compound 1a using 2-chloroacetyl chloridein the presence of aluminum trichloride (AlCl3) to yield compound 2aand
(2) then reacting compound 2a to displace the 2-chloroketone by the sodium salt of the N-formyl sulfonamide in the presence of a tetraalkyl ammonium halide to yield the amino-ketone compound 3aand
(3) reacting the compound 3a within the presence of sulfuric acid to yield the compound 4aand
(4) performing a Pictet-Spengler cyclization with formaldehyde, catalyzed by trifluoroacetic acid to yield the ketone compound 5aand
(5) treating compound 5a with trimethylorthoformate (TMOF) and acid in the presence of a radical initiator to produce the 6-azaindole compound 6aand
(6) oxidizing the pyridine nitrogen on compound 6a using hydrogen peroxide (H2O2) and phthalic anhydride to yield the N-oxide compound 7aand
(7) treating compound 7a with PyBrop in the presence of bases K3PO4 and NaOH to yield the bromo-azaindole compound 8aand
(8) then acylating onto the C3 of the indole group of compound 8a to produce the oxalate compound 9aand
(9) coupling compound 9a with N-benzoyl piperazine to yield the amide compound 10aand
(10) adding the triazole groupto compound 10a using copper catalysis in the presence of ligand and base to produce the compound 11aand
(11) the optional formation of 11b or 11c from compound 11a (12) alkylating the indole nitrogen of compound 11a, 11b or 11c using the chloro-phosphate compoundto provide the phosphate ester compound 12aand
(13) performing a sovolysis of the tert-butyl groups of compound 12a to yield the final compound 13a.